Absence of both MDR1 (ABCB1) and Breast Cancer Resistance Protein (ABCG2) Transporters Significantly Alters Rivaroxaban Disposition and Central Nervous System Entry

Basic and Clinical Pharmacology and Toxicology

Volumn 112, Issue 3, 2013, Pages 164-170

  Gong, Inna Y ^a   Mansell, Sara E ^a   Kim, Richard B ^a  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BREAST CANCER RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; RIVAROXABAN; ZOSUQUIDAR;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CLEARANCE; DRUG DISPOSITION; DRUG PENETRATION; DRUG TRANSPORT; IN VITRO STUDY; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; WILD TYPE;

ADMINISTRATION, ORAL; ANIMALS; ANTICOAGULANTS; ATP-BINDING CASSETTE TRANSPORTERS; CACO-2 CELLS; CELL MEMBRANE PERMEABILITY; CENTRAL NERVOUS SYSTEM; HUMANS; MALE; METABOLIC CLEARANCE RATE; MICE; MICE, KNOCKOUT; MORPHOLINES; P-GLYCOPROTEIN; SUBSTRATE SPECIFICITY; THIOPHENES; TISSUE DISTRIBUTION;

MUS;

EID: 84873706033     PISSN: 17427835     EISSN: 17427843     Source Type: Journal    
DOI: 10.1111/bcpt.12005     Document Type: Article

References (27)

1. Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008;451:914-8.
2. Eriksson BI, Quinlan DJ, Eikelboom JW. Novel oral factor Xa and thrombin inhibitors in the management of thromboembolism. Annu Rev Med 2011;62:41-57.
3. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e44S-88S.
4. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development. Clin Pharmacokinet 2009;48:1-22.
5. Fox KA, Piccini JP, Wojdyla D, Becker RC, Halperin JL, Nessel CC et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J 2011;32:2387-94.
6. Degorter MK, Xia CQ, Yang JJ, Kim RB. Drug transporters in drug efficacy and toxicity. Annu Rev Pharmacol Toxicol 2012;52:249-73.
7. Staud F, Pavek P. Breast cancer resistance protein (BCRP/ABCG2). Int J Biochem Cell Biol 2005;37:720-5.
8. Schinkel AH, Wagenaar E, Mol CA, van Deemter L. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest 1996;97:2517-24.
9. Gnoth MJ, Buetehorn U, Muenster U, Schwarz T, Sandmann S. In vitro and in vivo P-glycoprotein transport characteristics of rivaroxaban. J Pharmacol Exp Ther 2011;338:372-80.
10. Krishnamurthy P, Schuetz JD. Role of ABCG2/BCRP in biology and medicine. Annu Rev Pharmacol Toxicol 2006;46:381-410.
11. Kodaira H, Kusuhara H, Ushiki J, Fuse E, Sugiyama Y. Kinetic analysis of the cooperation of P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp/Abcg2) in limiting the brain and testis penetration of erlotinib, flavopiridol, and mitoxantrone. J Pharmacol Exp Ther 2010;333:788-96.
12. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR et al. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos 2000;28:655-60.
13. Rabindran SK, Ross DD, Doyle LA, Yang W, Greenberger LM. Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res 2000;60:47-50.
14. Mease K, Sane R, Podila L, Taub ME. Differential selectivity of efflux transporter inhibitors in Caco-2 and MDCK-MDR1 monolayers: a strategy to assess the interaction of a new chemical entity with P-gp, BCRP, and MRP2. J Pharm Sci 2012;101:1888-97.
15. Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X et al. Membrane transporters in drug development. Nat Rev Drug Discov 2010;9:215-36.
16. Sinnaeve PR, Brueckmann M, Clemens A, Oldgren J, Eikelboom J, Healey JS. Stroke prevention in elderly patients with atrial fibrillation: challenges for anticoagulation. J Intern Med 2012;271:15-24.
17. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W. Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology 2007;52:333-46.
18. Schinkel AH. P-Glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Deliv Rev 1999;36:179-94.
19. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ et al. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res 1999;16:408-14.
20. Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D. Metabolism and excretion of rivaroxaban, an oral, direct factor Xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos 2009;37:1056-64.
21. Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross DD et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 2000;113(Pt 11):2011-21.
22. Urquhart BL, Ware JA, Tirona RG, Ho RH, Leake BF, Schwarz UI et al. Breast cancer resistance protein (ABCG2) and drug disposition: intestinal expression, polymorphisms and sulfasalazine as an in vivo probe. Pharmacogenet Genomics 2008;18:439-48.
23. Bailey KM, Romaine SP, Jackson BM, Farrin AJ, Efthymiou M, Barth JH et al. Hepatic metabolism and transporter gene variants enhance response to rosuvastatin in patients with acute myocardial infarction: the GEOSTAT-1 Study. Circ Cardiovasc Genet 2010;3:276-85.
24. Sadeque AJ, Wandel C, He H, Shah S, Wood AJ. Increased drug delivery to the brain by P-glycoprotein inhibition. Clin Pharmacol Ther 2000;68:231-7.
25. Cervera A, Amaro S, Chamorro A. Oral anticoagulant-associated intracerebral hemorrhage. J Neurol 2012;259:212-24.
26. Bauer KA. Reversal of antithrombotic agents. Am J Hematol 2012;87 (Suppl 1):S119-26.
27. Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med 2012;366:864-6.